RELATIONSHIP BETWEEN LIPID METABOLISM AND INSULIN-MEDIATED GLUCOSE DISPOSAL

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It is well known that the availability of fatty acids for oxidation at the cellular level might be responsible for alterations in carbohydrate metabolism. While some studies have shown that changes in free fatty acid concentrations are accompanied by reciprocal changes in whole body glucose oxidation, it is not clear whether total insulin mediated glucose disposal may be correlated to changes in metabolism. This study combines the techniques of the euglycemic clamp, indirect calorimetry, and labeled free fatty acid technique to determine the relationship between insulin mediated glucose disposal, glucose oxidation and storage and measures of lipid metabolism. In vitro adipocyte data is collected from adipocytes isolated by open abdominal fat biopsy from the same subjects. Subjects are studied over a range of obesity to provide a range of lipid metabolic profiles and insulin resistance. The results suggest a direct interaction between lipid oxidation and glucose oxidation in vivo. However, this interrelationship can only partially explain impaired in vivo insulin mediated glucose disposal, since the former decreases per gm of fat as obesity increases whereas the latter increases. This implies that several neurologic or hormonal factors may interact to regulate FFA release from adipose tissue in obese individuals. Finally, a large non-oxidative component of FFA turnover has been observed which far exceeds the rate of VLDL triglyceride production. This component may be important in the regulation of FFA metabolism in vivo.